DeCure for Developmental and epileptic encephalopathy, 66
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 66 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDevelopmental and epileptic encephalopathy, 66 maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for developmental and epileptic encephalopathy, 66 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Developmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders defined by drug-resistant seizures and neurodevelopmental delay, typically beginning in infancy or early childhood and carrying a generally poor prognosis. The concept rests on the assumption that aggressive epileptic activity during brain maturation is the main causal factor in cognitive and neuropsychological impairment or regression. Diagnosis criteria are not well developed and treatment options have been described as very limited, with clinicians often unable to distinguish benign epileptic syndromes. The understanding of DEE has evolved from initial genetic underpinnings to a clinically driven term encompassing a broader group of aetiologies, and it is especially important to recognise treatable or modifiable entities within this group.
A retrospective study from 2020 to 2023 examined pulse intravenous methylprednisolone (IVMP) therapy in 21 paediatric patients with epileptic encephalopathy, all aged 18 years or younger at the time of treatment and with at least six months of follow-up. The responder rate, defined as seizure reduction greater than 50%, was 85.7% at six and nine months of therapy, and 80.9% at six months after therapy suspension. Genetic aetiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy. The fourth month of therapy was the minimum time point to establish effectiveness. All patients showed improvements in quality of life, EEG tracing and postural-motor development, and no relevant adverse events were observed.
Other reviews summarise currently well-established DEE syndromes and available precision therapies, but do not report original trial data. One case report describes a child whose treatment-responsive focal epilepsy evolved between 18 months and 3 years into treatment-resistant focal epilepsy with an epileptic encephalopathy, illustrating poorly understood age-related changes in seizure susceptibility, seizure types and drug responsiveness. The overall prognosis for DEE remains poor, and the evidence base for most interventions is limited to small retrospective series.
What is still missing are large prospective trials, standardised diagnostic criteria that can be applied consistently across centres, and reliable methods to stratify patients by genetic aetiology or EEG pattern before treatment begins. Funding for multicentre studies and long-term follow-up of developmental outcomes, rather than seizure counts alone, is needed to determine whether any intervention durably alters the course of the encephalopathy rather than merely suppressing seizures.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Medicine Science and the Law · 1964 · 119 citations
The Neuropathology of Status Epilepticus
AbstractA description is given of the clinical and neuropathological findings in eleven cases of status epilepticus in young children. The distribution of ischaemic nerve cell changes in cerebral cortex, hippocampus, basal ganglia, and cerebellum, conform to the pattern of post-ictal brain damage described by Scholz. The same changes are found in brains showing oedema as in those without. Reasons are given for discounting the theory that vascular compression plays a decisive part in the pathogenesis of this type of encephalopathy.
Epileptic encephalopathies: Optimizing seizure control and developmental outcome
AbstractCognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes.
Human Genome Variation · 2014 · 18 citations · open access
A novel KCNT1 mutation in a Japanese patient with epilepsy of infancy with migrating focal seizures
AbstractEpilepsy of infancy with migrating focal seizures (EIFMS) is a rare, early-onset epileptic encephalopathy characterized by polymorphous focal seizures. De novo mutations of KCNT1 have been identified in cases of this disorder. We encountered a sporadic patient with EIFMS, who suffered tonic convulsions at the age of 9 days. Using Sanger sequencing, we identified a de novo missense mutation of the same amino acid affected by a previously identified mutation, c.1420C>T (p.Arg474Cys).
International Journal of Epilepsy · 2025 · 1 citations · open access
Developmental and Epileptic Encephalopathies: Progress in Understanding and Clinical Implications
AbstractAbstract Developmental and epileptic encephalopathies (DEEs) are a group of complex pediatric epilepsies associated with adverse neurodevelopmental outcomes and multiaxial neurological morbidities. The understanding of DEE has evolved from its initial genetic underpinnings, to a clinically driven term encompassing a broader group of etiologies. Although individually rare, the DEEs constitute a sizeable group of pediatric epilepsies. It is especially important to recognize treatable or modifiable entities in this group. This review attempts to highlight the progress in understanding, along with the evolution of the conceptual framework of DEEs. A summary of the currently well-established DEE syndromes is provided along with available precision therapies, which might help the treating physician in the appropriate evaluation and management of the affected children.
Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration
AbstractAbstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.
DOAJ (DOAJ: Directory of Open Access Journals) · 2024 · 0 citations
Research progress on developmental and epileptic encephalopathy
AbstractDevelopmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders characterized by drug-resistant seizures and neurodevelopmental delay, which can hinder brain development and lead to severe cognitive, behavioral, and motor impairments. DEE is mainly driven by genetic factors, typically with an onset in infancy or early childhood and generally with an overall poor prognosis. This article provides a review of the definition, epilepsy syndromes, genetic etiology, and precision treatment of DEE.
NATIONAL JOURNAL OF NEUROLOGY · 2013 · 0 citations · open access
On the Clinics and Diagnosis of Epileptic Encephalopathy
AbstractEarly childhood is characterized by a continuous process of development of structures and functions of organism, especially central nervous system.The concept of epileptic encephalopathy is based on the assumption that the aggressive epileptic activity during the maturation of the brain is the main causal factor in cognitive and neuropsychological impairment or regress. With age, EEG signs of evolving consistent with the transition into each another. Currently the diagnosis criteria are not well developed and the treatment options are very limited, whereby patients cannot receive adequate treatment that further aggravates encephalopathy. Unfortunately clinicians are often unable to diagnose also benign epileptic syndromes.
A Child with Epilepsy: Initial Presentation and Subsequent Course
AbstractPresented is the case of a child with epilepsy with dramatic evolution between the ages of 18 months and 3 years. Initially, the case is one of treatment-responsive focal epilepsy, but then evolves to treatment-resistant focal epilepsy with an epileptic encephalopathy. The case demonstrates the poorly understood entities of age-related changes in seizure suspectibility, seizure types, and drug responsiveness.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
